Diastolic pressure gradient predicts outcome in patients with heart failure and preserved ejection fraction

Purpose:

Pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF) is associated with poor outcome. According to the diastolic pressure gradient (DPG) with a cut-off of 7 mmHg, affected patients can be further sub-classified into isolated postcapillary PH (Ipc-PH) and combined pre- and pc-PH (Cpc-PH). However, the clinical significance and prognostic value of DPG remains to be elucidated.

Methods:

Patients with HFpEF diagnosed according to current ESC guidelines were enrolled in our prospective registry. Borderline PH was defined as a mean pulmonary arterial pressure (mPAP) between 21 – 24 mmHg, and manifest PH was diagnosed, if mPAp ≥25 mmHg. DPG was calculated as difference between diastolic PAP and mean pulmonary arterial wedge pressure. Hospitalization for HF and death for cardiac reason were defined as the primary study endpoint.

Results:

Between December 2010 and December 2014, 193 HFpEF patients were registered. 19 patients refused right heart catheter and were excluded. Of the remaining 174 patients, 11 (6.3%) had no PH, 15 (8.6%) had borderline PH and 148 (85.1%) a manifest PH. PH patients (66% females, mean age 70 ± 7 years) were further sub-classified into Ipc-PH (n = 126) and Cpc-PH (n = 22).

Patients with a Cpc-PH had a shorter six-minute walk distance (253.5 ± 128.7 m vs. 318.4 ± 117.1 m; p = 0.021), a higher NT-proBNP (3816.9 ± 5977.8 pg/ml vs. 1651.6 ± 1883.5 pg/ml; p = 0.001), larger right ventricles (42.1 ± 8.9 mm vs. 37.4 ± 7.1 mm, p = 0.010) and a lower capillary partial pressure of oxygen (63.4 ± 9.8 mmHg vs. 73.3.± 11.6 mmHg; p = 0.001) compared to patients with Ipc-PH. During a median follow-up time of 25.2 months, 55 patients (33.7%) reached the combined endpoint. DPG was found to be an independent predictor of outcome (HR 1.167, 95% CI 1.047 – 1.299; p = 0.005). The worst outcome was recognized in the group of patients with Cpc-PH, as compared to Ipc-PH patients (log rank test, p = 0.015).

Conclusion:

The presence of PH in HFpEF is associated with adverse outcome. The subgroup with Cpc-PH had a worse clinical status and event-free survival as compared to the remainder of the group. Although it remains unclear which subset of patients is prone to develop superimposed pulmonary vasculature remodeling, our data indicate a potential contribution of hypoxemia.